Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients


Eugenio Picano, MD, PhD, CNR, Institute of Clinical Physiology, via Moruzzi, 1, 56123 Pisa, Italy (fax: 0039-050-3152374; e-mail:


Background.  Heart failure is characterized by chronically increased adenosine levels, which are thought to express a protective anti-heart failure activation of the adenosinergic system. The aim of the study was to assess whether the activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can be mirrored by a blunted increase in plasma adenosine concentration following dipyridamole stress, which accumulates endogenous adenosine.

Methods.  Two groups were studied: IDC patients (n = 19, seven women, mean age 60 ± 12 years) with angiographically confirmed normal coronary arteries and left ventricular ejection fraction <35%; and normal controls (n = 15, six women, mean age 68 ± 5 years). Plasma adenosine was assessed by high-performance liquid chromatography methods in blood samples from peripheral vein at baseline and 12 min after dipyridamole infusion (0.84 mg kg−1 in 10 min).

Results.  At baseline, IDC patients showed higher plasma adenosine levels than controls (276 ± 27 nm L−1 vs. 208 ± 48 nm L−1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma adenosine levels than controls (322 ± 56 nm L−1 vs. 732 ± 250 nm L−1, P < 0.001). The dipyridamole-induced percentage increase in plasma adenosine over baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine levels found in normal subjects.

Conclusion.  Patients with IDC have abnormally high baseline adenosine levels and – even more strikingly – blunted plasma adenosine increase following dipyridamole infusion. This is consistent with a chronic activation of the adenosinergic system present in IDC, which can be measured noninvasively in the clinical theatre.